Biology subjects

Soto, A.

Publications and source records attributed to Soto, A..

26 records · Page 2Linked to original sources

bioRxiv2022

Qualitative and quantitative analysis of the constitutive bark of Q. ilex x Q. suber hybrids

Hybridization and introgression between cork oak (Quercus suber) and holm oak (Q. ilex) have traditionally been reckoned as undesirable processes, since hybrid individuals lack the profitable bark characteristics of cork oak. Nevertheless, a systematic and quantitative description of the bark of these hybrids at the microscopic level based on a significant number of individuals was not available to date. In this work we provide such a qualitative and quantitative description, identifying the most relevant variables for their classification. Hybrids show certain features intermediate between those of the parent species, as well as other unique features, as the general suberization of inactive phloem, reported here for the first time. These results suggest a relevant hybridization-induced modification of the genetic expression patterns. Therefore, hybrid individuals provide a valuable material to disentangle the molecular mechanisms underpinning bark development in angiosperms.

plant biology↗

bioRxiv2022

STEREOLOGICAL EVALUATION OF TISSUE PRESERVATION AFTERNEUROPROTECTIVE TREATMENTS FOR TRAUMATIC SPINAL CORDINJURY

Spinal cord injury (SCI) is a major cause of permanent disability and its causes and pathophysiological effects are very variables between patients. The assessment of tissue damage extent and neurodegeneration degree correlated with the functional evaluation are the most accepted tools to diagnose and prognose the trauma severity. Animal models of SCI have been used for treatment development and in the present work we evaluate the potency of stereological tools to estimate damage degree for a diagnostic of neural degeneration and locomotor and sensorial disability after SCI and the efficacy of different types of therapeutic strategies.

neuroscience↗

bioRxiv2022

MiR-182-5p regulates Nogo-A expression and promotes neurite outgrowth of hippocampal neurons in vitro

Nogo-A protein is a key myelin-associated inhibitor for axonal growth, regeneration, and plasticity in the central nervous system (CNS). Regulation of the Nogo-A/NgR1 pathway facilitates functional recovery and neural repair after spinal cord trauma and ischemic stroke. MicroRNAs are described as effective tools for the regulation of important processes in CNS such as neuronal differentiation, neuritogenesis, and plasticity. Our results showed that miR-182-5p mimic specifically downregulates the expression of the luciferase reporter gene fused to the mouse Nogo-A 3UTR, and Nogo-A protein expression in Neuro-2a and C6 cells. Finally, we observed that when rat primary hippocampal neurons are co-cultured with C6 cells transfected with miR-182-5p mimic, there is a promotion of the outgrowth of neuronal neurites in length. From all these data we suggest that miR-182-5p may be a potential therapeutic tool for the promotion of axonal regeneration in different diseases of the CNS. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/482803v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@e0979forg.highwire.dtl.DTLVardef@10265eborg.highwire.dtl.DTLVardef@71603dorg.highwire.dtl.DTLVardef@1654818_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBioinformatics analyses show that miR-182-5p targets Nogo-A 3UTR. C_LIO_LIMiR-182-5p downregulates Nogo-A protein expression in murine cell lines. C_LIO_LIMiR-182-5p promotes neurite outgrowth of rat primary hippocampal neurons in vitro. C_LIO_LIMiR-182-5p is suggested as a potential therapeutic tool for the promotion of axonal regeneration in different pathologies/diseases of the central nervous system. C_LI

neuroscience↗

bioRxiv2022

First report of kdr L1014F and ace-1 G119S insecticide resistance in Belgian Culex mosquitoes

The emergence of West Nile virus and Usutu virus in Europe poses a significant risk to public health. In the absence of efficient antiviral therapy or vaccine candidates, the only strategy to control these arboviruses is to target the Culex (Diptera: Culicidae) mosquito vector. However, the selection pressure caused by exposure to insecticides for vector control or agricultural pest control can lead to insecticide resistance, thereby reducing the efficacy of insecticide-based vector control interventions. In Culex mosquitoes, two of the most common amino acid substitutions associated with insecticide resistance are the kdr L1014F in voltage gated sodium channels and G119S in acetylcholinesterase. In this study, Culex pipiens biotype pipiens, Culex torrentium, and Culex modestus were sampled from 2019 to 2021 in three distinct environmental habitats (urban, peri-urban, and agricultural) in and around the city of Leuven, Belgium. Individual mosquitoes were screened for two mutations resulting in L1014F and G119S amino acid substitutions. Both mutations were observed in Culex pipiens and Culex modestus but not in Culex torrentium mosquitoes across the four collection sites. Furthermore, multi-resistance or cross-resistance in Culex pipiens could be a threat in these areas, as both mutations were observed at low frequencies. These results provide the first report of kdr L1014F and ace-1 G119S resistance in Culex pipiens and Culex modestus mosquitoes from Belgium, highlighting the importance of mosquito surveillance to design effective arbovirus outbreak control strategies.

molecular biology↗

bioRxiv2021

A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric hAdV5 vector. The vaccine (named CoroVaxG.3) is based on three pillars: i) high expression of Spike to enhance its immunodominance by using a potent promoter and a mRNA stabilizer; ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; iii) use of Spike stabilized in a prefusion conformation. Transduction with CoroVaxG.3 expressing Spike (D614G) dramatically enhanced Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3 vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha) and P.1 (gamma) Spikes, as well as an authentic WT and P.1 SARS-CoV-2 isolates. Neutralizing antibodies did not wane even after 5 months making this kind of vaccine a likely candidate to enter clinical trials

immunology↗

bioRxiv2021

Allelic and Genotypic Frequencies of NAT2, CYP2E1 and AADAC genes in a cohort of Peruvian Tuberculosis Patients

BackgroundWe determined the frequency of genetic polymorphisms in three anti-TB drug metabolic proteins previously reported: N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1) and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. We included 395 participants completed their anti-tuberculosis treatment. Results[~]74% of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6 and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug-induced liver injuries. [~] 64% are homozygous for the wild-type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug-resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in in European American, African American, Japanese, and Korean populations. ConclusionsThis high prevalence of slow metabolizers for Isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.

genetics↗

bioRxiv2021

Mobile microscopy and telemedicine platform assisted by deep learning for quantification of Trichuris trichiura infection.

Soil-transmitted helminths (STH) are the most prevalent pathogens among the group of neglected tropical diseases (NTDs). Kato-Katz technique is the diagnosis method recommended by WHO and although is generally more sensitive than other microscopic methods in high transmission settings, it often presents a decreased sensitivity in low transmission settings and it is labour intensive. Digitizing the samples could provide a solution which allows to store the samples in a digital database and perform remote analysis. Artificial intelligence methods based on digitized samples can support diagnostics efforts by support diagnostics efforts by performing an automatic and objective quantification of disease infection. In this work, we propose an end-to-end pipeline for microscopy image digitization and automatic analysis of digitized images of soil-transmitted helminths. Our solution includes (1) a digitalization system based on a mobile app that digitizes the microscope samples using a low-cost 3D-printed microscope adapter, (2) a telemedicine platform for remote analysis and labelling and (3) novel deep learning algorithms for automatic assessment and quantification of parasitological infection of STH. This work has been evaluated by comparing the STH quantification using both a manual remote analysis based on the digitized images and the AI-assisted quantification against the reference method based on conventional microscopy. The deep learning algorithm has been trained and tested on 41 slides of stool samples containing 949 eggs from 6 different subjects using a cross-validation strategy obtaining a mean precision of 98,44% and mean recall of 80,94%. The results also proved the potential of generalization capability of the method at identifying different types of helminth eggs. In conclusion, this work has presented a comprehensive pipeline using smartphone-based microscopy integrated with a telemedicine platform for automatic image analysis and quantification of STH infection using artificial intelligence models.

microbiology↗

bioRxiv2018

Vitamin D3 regulates estrogen’s action and affects mammary epithelial organization in 3D cultures

Vitamin D3 (vitD3) and its active metabolite, calcitriol (1,25-(OH)2D3), affect multiple tissue types by interacting with the vitamin D receptor (VDR). Although vitD3 deficiency has been correlated with increased incidence of breast cancer and less favorable outcomes across ethnic groups and latitudes, randomized human clinical trials have yet to provide conclusive evidence on the efficacy of vitD3 in treating and/or preventing breast cancer. When considering that carcinogenesis is \"development gone awry\", it becomes imperative to understand the role of vitD3 during breast development. Mammary gland development in VDR KO mice is altered by increased ductal elongation and lateral branching during puberty, precocious and increased alveologenesis at pregnancy and delayed post-lactational involution. These developmental processes are largely influenced by mammotropic hormones, i.e., ductal elongation by estrogen, branching by progesterone and alveologenesis by prolactin. However, research on vitD3s effects on mammary gland morphogenesis focused on cell proliferation and apoptosis in 2D culture models and utilized supra-physiological doses of vitD3, conditions that spare the microenvironment in which morphogenesis takes place. Here, using two 3D culture models, we investigated the role of vitD3 in mammary epithelial morphogenesis. We found that vitD3 interferes with estrogens actions on T47D human breast cancer cells in 3D differently at different doses, and recapitulates what is observed in vivo. Also, vitD3 can act autonomously and affect the organization of MCF10A cells in 3D collagen matrix by influencing collagen fiber organization. Thus, we uncovered how vitD3 modulates mammary tissue organization independent of its already known effects on cell proliferation.

developmental biology↗